Aldehyde Wolff-Kishner reaction

A useful variant of the imine-forming reaction just discussed involves the treatment of an aldehyde or ketone with hydrazine, H2NNH2, in the presence of KOH. Called the Wolff-Kishner reaction, the process is a useful and genera method for converting an aldehyde or ketone into an alkane, r2c=o —> R2CH2. 

Wolff-Kishner reaction (Section 19.9) The conversion of an aldehyde or ketone into an alkane by reaction with hydrazine and base. 

Hydrogenolysis of an aldehyde or ketone carbonyl to >CH2 is an important organic transformation, and classical procedures such as the Clemmenson and Wolff-Kishner reactions have limitations (24, 25) heterogeneous catalytic systems and several two-step procedures are also known (1, 24, 26). Our observation of this conversion in what is essentially a 2-phase medium... 

Alkanes, RH (Sec. 7.7) (Sec. 10.7) (Sec. 10.8) (Sec. 19.9) from alkenes by catalytic hydrogenation from alkyl halides by protonolysis of Grignard reagents from alkyl halides by coupling with Gilman reagents from ketones and aldehydes by Wolff-Kishner reaction... 

Hydrazine, H2NNH2 Reacts with ketones or aldehydes in the presence of KOH to yield the corresponding alkanes (Wolff-Kishner reaction Section 19.10). 

Direct transition from level 2 to level 0 can be achieved by way of the Wolff-Kishner reaction (treatment of the respective hydrazones with alkali), a classical pathway for the reduction of carbonyl compounds. At the same time, a direct conversion of aldehydes and ketones into alkenes is also feasible via reductive cleavage of their tosylhydrazones under the action of MeLi, the Shapiro reaction (Scheme 2.63). "... 

Wolff-Kishner reaction. This reduction reaction was discovered independently in Germany (Wolff, 1912) and in Russia (Kishner, 1911). A ketone (or aldehyde) is converted into the hydra-zone, and this derivative is heated in a sealed tube or an autoclave with sodium ethoxide in absolute ethanol. 

The reaction of hydrazine with a,/S-unsaturated aldehydes and ketones (the anomalous Wolff-Kishner reaction, Houben-Weyl, Vol. 4/3, p71) sometimes provides a one-pot procedure in which the cyclopropane is formed directly, but often the intermediate 2,3-dihydro-l//-pyrazole is isolated and heated either alone or with a basic catalyst to effect elimination of nitrogen. Hence in the conversion of chalcone to 1,2-diphenylcyclopropane the intermediate 3,5-diphenyl-2,3-dihydro-l//-pyrazole (10) was isolated and heated with potassium hydroxide. 

The normal reactivity of carbonyl derivatives (e.g., hydrazone formation of aldehydes, Wolff-Kishner reduction of ketones to alkylpyridazines, sodium in ethanol reduction of ketones to alcohols) was very briefly discussed in CHEC-I <84CHEC-i(3B)l>. Some examples of reactions are given here. 

A method of almost universal applicability for the deoxygenation of carbonyl compounds is the Wolff-Kishner reduction While the earlier reductions were carried out in two steps on the derived hydrazone or semicarbazone derivatives, the Huang-Minlon modification is a single-pot operation. In this procedure, the carbonyl compound and hydrazine (hydrate or anhydrous) are heated (180-220 °C) in the presence of a base and a proton source. Sodium or potassium hydroxide, potassium-t-butoxide and other alkoxides are the frequently used bases and ethylene glycol or its oligomers are used as the solvent and proton source. Over the years, several modifications of this procedure have been used to cater to the specific needs of a given substrate. The Wolff-Kishner reaction works well with both aldehydes and ketones and remains the most routinely used procedure for the preparation of alkanes from carbonyl compounds (Table 9). This method is equally suitable for the synthesis of polycyclic and hindered alkanes. 

The third example in Table 9.4, that is, 3a-c, where G = NH2, describes the addition of hydrazine (H2NNH2) and substituted hydrazines (ArNHNH2) to the carbonyl (C=0) to produce the corresponding hydrazones ( hydrazine derivatives ) of the aldehyde or ketone with which the reaction began. It will be remembered that the hydrazone derived from hydrazine (H2NNH2) itself has already been encountered during the discussion of the reduction of ketones to alkanes (Scheme 9.12) as part of the Wolff-Kishner reaction sequence vide supra). 

Reduction of aldehydes or ketones to hydrocarbons can be accomplished using the Clemmensen reaction (Zn/Hg/HCI), the Wolff-Kishner reaction (hydrazine, KOH), Raney nickel/Hj reduction of a dithioacetal, or palladium-catalyzed hydrogenolysis (aryl ketones only). 

Table 17 2 summarizes the reactions of aldehydes and ketones that you ve seen m ear her chapters All are valuable tools to the synthetic chemist Carbonyl groups provide access to hydrocarbons by Clemmensen or Wolff-Kishner reduction (Section 12 8) to alcohols by reduction (Section 15 2) or by reaction with Grignard or organolithmm reagents (Sections 14 6 and 14 7)... 

Another important synthetic method for the reduction of ketones and aldehydes to the corresponding methylene compounds is the Woljf-Kishner reduction. This reaction is carried out under basic conditions, and therefore can be applied for the reduction of acid-sensitive substrates it can thus be regarded as a complementary method. The experimental procedure for the Clemmensen reduction is simpler however for starting materials of high molecular weight the Wolff-Kishner reduction is more successful. 

The classical procedure for the Wolff-Kishner reduction—i.e. the decomposition of the hydrazone in an autoclave at 200 °C—has been replaced almost completely by the modified procedure after Huang-Minlon The isolation of the intermediate is not necessary with this variant instead the aldehyde or ketone is heated with excess hydrazine hydrate in diethyleneglycol as solvent and in the presence of alkali hydroxide for several hours under reflux. A further improvement of the reaction conditions is the use of potassium tcrt-butoxide as base and dimethyl sulfoxide (DMSO) as solvent the reaction can then proceed already at room temperature. ... 

The deoxygenation of aldehydes and ketones to the corresponding hydrocarbons via the hydrazones is known as the Wolff-Kishner reduction.28 Various modifications of the original protocols have been suggested. One of the most useful is the Huang-Minlon modification, which substituted hydrazine hydrate as a safer and less expensive replacement of anhydrous hydrazine. In addition, diethylene glycol together with sodium hydroxide was used to increase the reaction... 

This silyl hydrazone formation-oxidation sequence was originally developed as a practical alternative to the synthesis and oxidation of unsubstituted hydrazones by Myers and Furrow [31]. The formation of hydrazones directly from hydrazine and ketones is invariably complicated by azine formation. In contrast, silyl hydrazones can be formed cleanly from /V,/V -bis(7< rt-butyldimethylsilyl)hydrazine and aldehydes and ketones with nearly complete exclusion of azine formation. The resulting silylhydrazones undergo many of the reactions of conventional hydrazones (Wolff-Kishner reduction, oxidation to diazo intermediate, formation of geminal and vinyl iodides) with equal or greater efficiency. It is also noteworthy that application of hydrazine in this setting may also have led to cleavage of the acetate substituents. 

An important reduction reaction is Wolff-Kishner reduction of carbonyl group on aldehydes and ketones to form hydrazone ... 

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